Today's treatment of chronic pain conditions rests mostly on the use of FANS, anaesthetics, opioids, antiepileptic drugs, and antidepressants (Jensen T S, Finnerup N B: Management of neuropathic pain. Curr Opin Support Palliat Care. 2007 August; 1(2):126-31; Dray A. Neuropathic pain: emerging treatments. Br J Anaesth. 2008 July; 101(1):48-58). Each one of these classes of drugs has serious drawbacks to the point that in the pharmacological industry the field is considered as a high unmet medical need. Incomplete efficacy, development of tolerance and addiction, serious side effects are all unwanted results of the present therapeutic regimes for the various forms of pain, particularly the one classified as of neuropathic nature.
Neuropathic pain (NP) is defined as the one caused by direct dysfunction of the nervous system (Jensen T S, Finnerup N B: Management of neuropathic pain. Curr Opin Support Palliat Care. 2007 August; 1(2):126-31; Dray A. Neuropathic pain: emerging treatments. Br J Anaesth. 2008 July; 101(1):48-58), as opposed to the inflammatory pain that is due to release of algogens by surrounding tissues. The inflammatory pain serves the function of calling the body's attention to the injured part, whereas NP does not serve any beneficial purpose. Through wind up mechanisms, NP has the tendency to ingravescence and become chronic. Of course, in clinical practice it is very common to see mixture of inflammatory and neuropathic forms of pain as prototypically illustrated by osteoarthritic patients.
Addiction (or dependency) may cause serious medical conditions when treatment is interrupted (Culberson J W, Ziska M. Prescription drug misuse/abuse in the elderly. Geriatrics. 2008; 63:22-31; Licata S C, Rowlett J K. Abuse and dependence liability of benzodiazepine-type drugs: GABA(A) receptor modulation and beyond. Pharmacol Biochem Behav. 2008; 90:74-89; Oulis P, Masdrakis V G, Karakatsanis N A, Karapoulios E, Kouzoupis A V, Konstantakopoulos G, Soldatos C R. Pregabalin in the discontinuation of long-term benzodiazepine use: a case-series. Int Clin Psychopharmacol. 2008; 23:110-2; McConnell J G. Benzodiazepine tolerance, dependency, and withdrawal syndromes and interactions with fluoroquinolone antimicrobials. Br J Gen Pract. 2008; 58:365-6; Ballantyne J C, Shin N S. Efficacy of opioids for chronic pain: a review of the evidence. Clin J Pain. 2008; 24:469-78).
Effectiveness of chronic pharmacological treatment in neuropsychiatric and chronic pain conditions is often hampered by the development of tolerance (McConnell J G. Benzodiazepine tolerance, dependency, and withdrawal syndromes and interactions with fluoroquinolone antimicrobials. Br J Gen Pract. 2008; 58:365-6; Zanotti A, Natolino F, Contarino A, Lipartiti M, Giusti P. Abecarnil enhances recovery from diazepam tolerance. Neuropharmacology. 1999; 38:1281-8; Gupta N, Bhargava V K, Pandhi P. Tolerance and withdrawal to anticonvulsant action of clonazepam: role of nitric oxide. Methods Find Exp Clin Pharmacol. 2000; 22:229-35; Barcs G, Halász P. Effectiveness and tolerance of clobazam in temporal lobe epilepsy. Acta Neurol Scand. 1996; 93:88-93) manifested by loss of efficacy that may be partly, but not always, compensated by an increased daily dose. This compensatory manoeuvre entails the risk of increased unwanted side effects eventually resulting in diminished compliance or abandonment of the treatment (Jensen, T S; Finnerup, N B: Management of neuropathic pain. Curr Opin Support Palliat Care (2007), 1(2): 126-31; Ballantyne J C, Shin N S: Efficacy of opioids for chronic pain: a review of the evidence. Clin J Pain (2008) 24:469-78).
Other drugs (notably, but not only antiepileptic drugs [AEDs]) and some anti depressant agents may induce their own metabolism, yet another cause of lower serum levels, shorter half life in the patients body and diminished efficacy (Andreasen A H, Brøsen K, Damkier P. A comparative pharmacokinetic study in healthy volunteers of the effect of carbamazepine and oxcarbazepine—on cyp3a4. Epilepsia. 2007, 48:4906; Perucca E. Clinically relevant drug interactions with antiepileptic drugs. Br J Clin Pharmacol. 2006; 61:246-55.).
In view of the above, it is evident that there is a need in the art to reduce the problems of the present therapeutic regimes.